BACKGROUND Through a RNAi synthetic lethal screen we have identified the protein SUMOylation pathway to be required for the viability of Ras mutant cancer cells. PURPOSE In this project we aim to address the following questions: 1. the mechanism by which the inhibition of SUMOylation pathway is synthetically lethal with Ras mutation; 2. which cellular proteins are differentially SUMOylated in Ras mutant cells; 3. How the changes in SUMOylation status in these cells affect their function in the context of Ras mutation SIGNIFICANT MATERIALS AND METHODS 1. shRNAs that target the SUMO E1 and E2 ligases. 2. Stable cell lines that express 6x His tagged proteins. 3. mass-spectrometry protocol for protein ID FY2010 ACCOMPLISHMENT We have generated shRNAs that target the SUMO E1 and E2 ligases and are in the process of testing their function. We have also generated cell lines stably expressing His-tagged SUMO1, SUMO2 and SUMO3 and we are in the process of testing these cells.